Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma.
Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP-1 KO) mice and their WT controls using an ovalbumin (OVA) asthma model. TIMP-1 KO mice, compared to WT controls, developed an asthma phenotype characterized by AHR, pronounced cellular lung infiltrates, greater reduction in lung compliance, enhanced Th2 cytokine mRNA and protein expression, and altered collagen lung content associated with enhanced MMP-9 activity. Our findings support the hypothesis that TIMP-1 plays a protective role by preventing AHR and modulating inflammation, remodeling, and cytokine expression in an animal model of asthma.
Sands
Mark F
MF
VA Western New York Healthcare System, Buffalo, NY 14215, USA. mfsands@buffalo.edu
Ohtake
Patricia J
PJ
Mahajan
Supriya D
SD
Takyar
Shervin S
SS
Aalinkeel
Ravikumar
R
Fang
Yisheng V
YV
Blume
Jessica W
JW
Mullan
Barbara A
BA
Sykes
Don E
DE
Lachina
Sandra
S
Knight
Paul R
PR
Schwartz
Stanley A
SA
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D006909:Hydroxyproline / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000276:immunology / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D007073:Immunoglobulin E; D010047:Ovalbumin; D006909:Hydroxyproline